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. 2022 Feb 9:11:756214.
doi: 10.3389/fonc.2021.756214. eCollection 2021.

Efficacy and Safety of Systemic Treatments Among Colorectal Cancer Patients: A Network Meta-Analysis of Randomized Controlled Trials

Tung Hoang  1 , Dae Kyung Sohn  2 , Byung Chang Kim  2 , Yongjun Cha  2 , Jeongseon Kim  1
Affiliations

Efficacy and Safety of Systemic Treatments Among Colorectal Cancer Patients: A Network Meta-Analysis of Randomized Controlled Trials

Tung Hoang et al. Front Oncol. .

Abstract

Background: Systemic treatments, namely, either monotherapy or combination therapy, are commonly administered to patients with advanced or metastatic colorectal cancer (CRC). This study aimed to provide the complete efficacy and safety profiles and ranking of systemic therapies for the treatment of unresectable advanced or metastatic CRC.

Methods: We searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception until June 30, 2021, and also the bibliographies of relevant studies. Randomized controlled trials comparing two or more treatments, namely, at least capecitabine, 5-fluorouracil, leucovorin, irinotecan, bevacizumab, cetuximab, oxaliplatin, or panitumumab were investigated. A network meta-analysis using the Bayesian approach was performed to compare the efficacy and safety of treatments. The surface under the cumulative ranking curve (SUCRA) was calculated for the probability of each treatment as the most effective. The overall response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), adverse events (AEs) grade ≥3, and serious adverse events (SAEs) were evaluated.

Results: One hundred two publications with 36,147 participants were assigned to 39 different treatments. Among 11 treatments with full information on six outcomes, FOLFIRI/FOLFOX/FOLFOXIRI + bevacizumab significantly improved both the ORR and DCR, compared to FOLFIRI. Although FOLFOX and FOLFIRI/FOLFOX + cetuximab significantly prolonged both OS and PFS, treatments were comparable in terms of AEs grade ≥3 and SAEs. The top highest SUCRA values were observed in the FOLFOXIRI + panitumumab group for ORR (96%) and DCR (99%), FOLFIRI + bevacizumab + panitumumab group for OS (62%) and PFS (54%), and FOLFOXIRI + bevacizumab group for AEs grade ≥3 (59%) and SAEs (59%) outcomes.

Conclusions: These findings suggest an available range of systemic treatment therapies with different efficacy and safety profiles with patients. Further investigations of the side effects and mutation status are required to confirm our findings.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42019127772.

Keywords: chemotherapy; colorectal cancer; metastasis; network meta-analysis; targeted therapy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
PRISMA flowchart for study selection.
Figure 2
Figure 2
Risk of bias summary for each included study.
Figure 3
Figure 3
Risk of bias graph across all the included studies.
Figure 4
Figure 4
Network geometry of treatments included in the final analysis. ORR, overall response rate; DCR, disease control rate; OS, overall survival; PFS, progression-free survival; AEs, adverse events; SAEs, serious adverse events; X, capecitabine; B, bevacizumab; C, cetuximab; F, 5-fluorouracil; I, irinotecan; L, leucovorin; O, oxaliplatin; P, panitumumab. The network plots are based on treatments in a connected network according to different types of outcomes. The size of the node indicates the number of participants receiving each treatment, and the thickness of the line illustrates the number of studies included each comparison.
Figure 5
Figure 5
Scatter plot showing differences in estimates obtained from fixed-effects, random-effects, and meta-regression models. ORR, overall response rate; DCR, disease control rate; OS, overall survival; PFS, progression-free survival; AEs, adverse events; SAEs, serious adverse events; FOLFIRI, 5-fluorouracil/leucovorin/irinotecan; FOLFOX, 5-fluorouracil/leucovorin/oxaliplatin; FOLFOFIRI, 5-fluorouracil/leucovorin/oxaliplatin/irinotecan; XELOX, capecitabine/oxaliplatin; XELIRI, capecitabine/irinotecan; Bmab, bevacizumab; Cmab, cetuximab; Pmab, panitumumab.
Figure 6
Figure 6
Treatment efficacy and safety compared with FOLFIRI. ORR, overall response rate; DCR, disease control rate; OS, overall survival; PFS, progression-free survival; AEs, adverse events; SAEs, serious adverse events.
Figure 7
Figure 7
First-line and second-line treatment ranking probabilities. ORR, overall response rate; DCR, disease control rate; OS, overall survival; PFS, progression-free survival; AEs, adverse events; SAEs, serious adverse events; X, capecitabine; B, bevacizumab; C, cetuximab; F, 5-fluorouracil; I, irinotecan; L, leucovorin; O, oxaliplatin; P, panitumumab.
Figure 8
Figure 8
SUCRA ranking plot and cluster analysis. ORR, overall response rate; DCR, disease control rate; OS, overall survival; PFS, progression-free survival; AEs, adverse events; SAEs, serious adverse events; X, capecitabine; B, bevacizumab; C, cetuximab; F, 5-fluorouracil; I, irinotecan; L, leucovorin; O, oxaliplatin; P, panitumumab.
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